1. Field of the Invention
This invention relates generally to fibrinogen bandages and arterial bleeding models and methods of making and using thereof. In particular, the present invention relates to a fibrinogen bandage having propyl gallate and a swine arterial bleeding model.
2. Description of the Related Art
The control of hemorrhage is the initial step in first aid and field trauma care. Although the basic approach to homeostasis has not changed significantly since the onset of modem medicine, new and more effective methods, such as fibrinogen dressings and bandages, are currently being researched. See Matthew, T. L., et al. (1990) Ann. Surgery 50:40-44; Ochsner, M. G., et al. (1990) J. Trauma 30:884-887; Lerner, R. (1990) J. Surg. Res. 48:165-181; Lebowitz, R. A. et al. (1995) Am. J. of Otology 16:172-174; Suzuki, Y., et al. (1995) Arch. Surg. 130:952-955; and Rousou, J., et al. (1989) J. Thorac. Cardiovasc. Surg. 97:194-203.
Fibrinogen dressings were first used by trauma surgeons during World War I when Grey and his colleagues made prepolymerized fibrin sheets and powders. During World War II, fibrin glue was created with prepolymerized Styrofoam-like sheets of fibrin and fibrin films by the United States military and the American Red Cross. Fibrin based dressings show a significant difference in controlling bleeding time and reducing blood loss when compared to a control. See Jackson, M., et al. (1996) J. of Surg. Res. 60:15-22; and Jackson, M., et al. (1997) Surg. Forum, XL, VIII:770-772.
Despite the efficacy of fibrinogen dressings in controlling hemorrhage, the use of fibrinogen dressings was discontinued as blood and serum borne diseases such as hepatitis and HIV was often transmitted since the dressings comprised purified human or animal fibrinogen or other purified blood products. See Holcomb, J. B., et al. (1997) Surgical Clinics of North America 77:943-952. In the past few years, however, there has been a renewed interest in fibrin based products for treating wounds as plasma purification techniques have nearly eliminated the risk of blood and serum borne diseases. Additionally, suitable recombinant fibrinogen is expected to be commercially available soon.
There are a few patents that are directed to fibrinogen bandages, however, these fibrinogen bandages suffer from many drawbacks. The component that makes fibrinogen bandages too expensive for commercial use is the fibrinogen which is presently purified from human plasma and lyophilized onto a matrix which forms the backing of the bandage. The more fibrinogen that is added to the backing, the better the bandage works in stopping bleeding. However, the more fibrinogen added to the backing, the more costly the bandage. Additionally, the more fibrinogen added to the backing may contribute to the fragility of bandages having the higher amount of fibrinogen. The more fragile the bandage, the more difficult to work with as the bandage easily crumbles and does not bend to conform to various wound sites.
It has been speculated that the selective incorporation of agents that modify the biochemical pathways involved in clot formation will stabilize the formed clot and promote local coagulation. However, not all agents that normally promote clot formation and coagulation improve clot formation and coagulation when incorporated on or in fibrinogen dressings or bandages. For example, ε-amino caproic acid which is an antifibrinolytic agent that impedes the destruction of fibrin by binding to the lysine binding sites of plasminogen would therefore be expected to provide a more stable clot. In fact, Amicar® is an ε-amino caproic acid formulation used clinically whereby oral doses are used to control hemorrhaging after prostatectomies, to prevent rebleeding after dental extractions in patients having hereditary bleeding disorders, and to prevent rebleeding after subarachnoid hemorrhaging. However, it has been found that ε-amino caproic acid incorporated in or on fibrinogen dressings or bandages actually decreased coagulation and clot formation as compared to fibrinogen bandages alone.
In addition, the quest to improve fibrinogen dressings or bandages and find suitable agents that promote coagulation and clot formation to be incorporated in or on the fibrinogen dressings has been hindered by the lack of an adequate arterial bleeding model. Prior art methods and models for studying clot formation and arterial bleeding have been inadequate as they do not provide a good control that may be standardized and used in comparative studies.
Thus, a need still exists for commercially viable and effective fibrinogen dressings or bandages and arterial bleeding models for the study of agents, methods, and devices that modulate coagulation and clot formation.